A Study of Oral Nitrate in Adults With Pulmonary Hypertension With Heart Failure and Preserved Ejection Fraction

Phase 1

Completed

• Conditions: Pulmonary; Hypertension; Heart Failure; Preserved Ejection Fraction
• Interventions: Drug: 15N Nitrate; Drug: 14N Nitrate

• Registration Number: NCT02980068
• Lead Sponsor: Gladwin, Mark, MD

Brief Summary

This is an open-label, single-center study to examine distinguishing features of the structure and function of the oral and gut microbiome in healthy adult normal volunteers compared to volunteers with PH-HFpEF in the breakdown of oral nitrate.

Detailed Description

We will enroll 60 Group II PH (PH-HFpEF) or Group I PAH patients and 60 matched healthy controls over three years. The Subjects will receive a single dose of one of the two study drugs, determined by whether they will participate in one study visit or two: 15N nitrate (1,000 mg) or 14N Sodium Nitrate: standard sodium nitrate, and all will receive one dose of CLA 3g. Twenty of the PH or PAH subjects and 20 of the control subjects willing to return for a follow up visit 24 hours after drug administration will receive 15N nitrate. All others will receive standard sodium nitrate. CLA will be obtained from GNC (General Nutrition Corporation) and given once.

Throughout the experiment, we will measure blood pressure, heart rate, and respiratory rate as well as co-oximetry. Plasma samples are collected at approximate times 0, 2, and 6 hrs post-drug administration. Urine will be collected at approximate times 0 and 6 hrs. We will examine plasma and urine nitrate and nitrite. The 40 subjects who return for a second visit 24 hours post-drug administration will provide an additional plasma and urine sample.

Study Timeline

• Study First Submitted: 2016-11-17
• Study First Submitted QC: 2016-12-01
• Study First Posted: 2016-12-02
• Study Start: 2017-08-28
• Primary Completion: 2022-02-25
• Study Completion: 2022-02-25
• Status Verified: 2022-03
• Last Update Submitted: 2022-03-21
• Last Update Posted: 2022-03-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 77

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
15N Nitrate	15N Nitrate	single 1,000mg dose of 15N nitrate with 3g of conjugated linoleic acid (CLA).
14N Sodium Nitrate	14N Nitrate	single 1,000mg dose of 14N sodium nitrate with 3g of conjugated linoleic acid (CLA)

Primary Outcome Measures

Name	Time	Method
Bacterial content of the oral microbiome	Saliva and tongue scraping will occur preceding administration of drug	Saliva and tongue scraping will be analyzed for bacterial makeup
Change in nitrate level in urine	Urine collected approx 0 & 6 hours after drug administration	The investigators will examine urine nitrate
Change in nitrate level in plasma	Approx 50cc of blood drawn approx 0, 2, & 6 hours after drug administration	The investigators will examine plasma nitrate
Bacterial content of gut microbiome	Stool collected before drug administration	Stool will be analyzed for bacterial makeup
Change in nitrite level in urine	Urine collected approx 0 & 6 hours after drug administration	The investigators will examine urine nitrite
Change in nitrite level in plasma	Approx 50cc of blood drawn approx 0, 2, & 6 hours after drug administration	The investigators will examine plasma nitrite

Secondary Outcome Measures

Name	Time	Method
Change in heart rate	Continuous over 6 hour study visit
Change in respiratory rate	Continuous over 6 hour study visit
Change in blood pressure	Frequently over 6 hour study visit
Change in hemoglobin concentration	Continuous over 6 hour study visit

Trial Locations

Locations (2)

Nydia Chien; 🇺🇸 Pittsburgh, Pennsylvania, United States

University of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States